LYSINE METABOLISM IN THE RAT BRAIN: BLOOD—BRAIN BARRIER TRANSPORT, FORMATION OF PIPECOLIC ACID AND HUMAN HYPERPIPECOLATEMIA

Abstract— Through the use of intravenous pulse injection of L‐[U‐ 14 C] lysine, the blood‐brain barrier transport of L‐lysine was studied. The uptake of L‐lysine plus metabolites in the brain remained essentially unchanged at approx 0.002–0.005 nmol/g in the low dose (3μg per kg body weight) injection, and 20–40 nmol/g in the high dose (30 mg/kg) injection throughout the time intervals of up to 60 min. The uptake of L‐lysine plus metabolites in the heart, however, decreased substantially from 0.03 to 0.003 nmol/g in the low dose injection and from 320 to 62 nmol/g in the high dose injection. The plasma to heart uptake ratio only decreased slightly through the 60 min period: from 6 to 2 in either the low or high dose L‐lysine injection. The plasma to brain uptake ratio, however, decreased rapidly from a high of 62 to a low of about 4 in either the low or high dose injection throughout the 60‐min time course. Study of labeled L‐pipecolate formation in the plasma and individual organs indicates that this compound was formed only in the brain to a significant level within 0.5 min of 14 C‐L‐lysine intravenous pulse injection. Labeled pipecolate was recovered from heart, liver, kidney and plasma in significant quantities only at 2 min or later after pulse‐injection. It is concluded that the blood‐brain barrier of L‐lysine in the rat is not particularly strong and that the rat brain may be primarily responsible for L‐pipecolate synthesis from L‐lysine. The possible etiology of human hyperpipecolatemia is also discussed in light of the current findings.